2022
A multiple sclerosis–protective coding variant reveals an essential role for HDAC7 in regulatory T cells
Axisa P, Yoshida T, Lucca L, Kasler H, Lincoln M, Pham G, Del Priore D, Carpier J, Lucas C, Verdin E, Sumida T, Hafler D. A multiple sclerosis–protective coding variant reveals an essential role for HDAC7 in regulatory T cells. Science Translational Medicine 2022, 14: eabl3651. PMID: 36516268, DOI: 10.1126/scitranslmed.abl3651.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalitisRegulatory T cellsHistone deacetylase 7Multiple sclerosisT cellsMouse modelFunction of Foxp3CD4 T cellsHigher suppressive capacityVivo modelingAutoimmune encephalitisEAE severityImmunosuppressive subsetAutoimmune diseasesImmunomodulatory roleSuppressive capacityImmune cellsDisease onsetDistinct molecular classesSusceptibility lociGenetic susceptibility lociSingle-cell RNA sequencingDisease riskPatient samplesProtective variants
2015
Genetic variants associated with autoimmunity drive NFκB signaling and responses to inflammatory stimuli
Housley WJ, Fernandez SD, Vera K, Murikinati SR, Grutzendler J, Cuerdon N, Glick L, De Jager PL, Mitrovic M, Cotsapas C, Hafler DA. Genetic variants associated with autoimmunity drive NFκB signaling and responses to inflammatory stimuli. Science Translational Medicine 2015, 7: 291ra93. PMID: 26062845, PMCID: PMC4574294, DOI: 10.1126/scitranslmed.aaa9223.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAllelesAutoimmunityCase-Control StudiesCD4-Positive T-LymphocytesCell NucleusCytokinesFemaleGenetic Predisposition to DiseaseHumansInflammationMaleMiddle AgedMultiple SclerosisNF-kappa BPolymorphism, Single NucleotideProtein TransportReceptors, Tumor Necrosis Factor, Type IRisk FactorsSex CharacteristicsSignal TransductionTime FactorsTumor Necrosis Factor-alphaConceptsB-cell leukemia 3Multiple sclerosisNegative regulatorInflammatory stimuliGenetic variantsWide association studyDisease susceptibility variantsNaïve CD4 T cellsRapid genetic screeningCD4 T cellsActivation of p65Transcription factor nuclear factor κBExpression of NFκBNuclear factor κBApoptosis 1Cellular inhibitorGG risk genotypeDegradation of inhibitorCentral regulatorAssociation studiesCytokine blockadeUlcerative colitisAutoimmune diseasesTumor necrosisSusceptibility variants
2010
TGF-β Induces IL-9 Production from Human Th17 Cells
Beriou G, Bradshaw EM, Lozano E, Costantino CM, Hastings WD, Orban T, Elyaman W, Khoury SJ, Kuchroo VK, Baecher-Allan C, Hafler DA. TGF-β Induces IL-9 Production from Human Th17 Cells. The Journal Of Immunology 2010, 185: 46-54. PMID: 20498357, PMCID: PMC2936106, DOI: 10.4049/jimmunol.1000356.Peer-Reviewed Original ResearchMeSH KeywordsAdultCell PolarityCells, CulturedCoculture TechniquesDiabetes Mellitus, Type 1Gene Expression RegulationHumansImmunohistochemistryInflammation MediatorsInterleukin-17Interleukin-9Middle AgedResting Phase, Cell CycleT-Lymphocytes, Helper-InducerTransforming Growth Factor beta1Young AdultConceptsCD4 T cellsIL-9 productionIL-17IL-9IL-1betaCD4 cellsProinflammatory cytokinesT cellsNaive cellsIL-9/ILCD4 T cell subsetsMemory CD4 T cellsNaive CD4 T cellsHuman naive CD4 T cellsTh17-inducing cytokinesT cell subsetsHuman autoimmune diseasesAutoimmune diabetesMemory CD4Th17 cellsTh2 cytokinesAutoimmune diseasesCell subsetsIL-4Inflammatory conditionsIL-12 induces human CD4+CD45RA-CD25hiCD127low/neg regulatory T cells to secrete IFNγ and IL-10 and acquire a non-regulatory effector phenotype (138.9)
Dominguez-Villar M, Hafler D, Baecher-Allan C. IL-12 induces human CD4+CD45RA-CD25hiCD127low/neg regulatory T cells to secrete IFNγ and IL-10 and acquire a non-regulatory effector phenotype (138.9). The Journal Of Immunology 2010, 184: 138.9-138.9. DOI: 10.4049/jimmunol.184.supp.138.9.Peer-Reviewed Original ResearchRegulatory T cellsT cellsEffector phenotypeTreg functionIL-10Immune responseHuman Treg functionCD4 T cellsT cell responsesIL-12 familyIL-12 inducesTreg suppressionPeripheral toleranceCytokine milieuT-betIFN-gammaTregsImmune systemCell responsesCytokinesRecent evidencePivotal roleCellsPhenotypeDistinct effects
2008
IL-21 and TGF-β are required for differentiation of human TH17 cells
Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA. IL-21 and TGF-β are required for differentiation of human TH17 cells. Nature 2008, 454: 350-352. PMID: 18469800, PMCID: PMC2760130, DOI: 10.1038/nature07021.Peer-Reviewed Original Research
2006
The Purification and Functional Analysis of Human CD4+CD25high Regulatory T Cells
Baecher-Allan C, Hafler DA. The Purification and Functional Analysis of Human CD4+CD25high Regulatory T Cells. Current Protocols In Immunology 2006, 72: 7.4b.1-7.4b.12. PMID: 18432975, DOI: 10.1002/0471142735.im0704bs72.Peer-Reviewed Original ResearchConceptsRegulatory T cellsCD4 T cellsT cellsHuman regulatory T cellsHuman CD4 T cellsLevels of CD25Suppressive featuresCD25Coculture assaysVitro proliferationHigh expressionVivo developmentEndogenous expressionSuch cellsCellsSmall percentageMouse cellsHigh levelsAutoimmunityHumansExpressionMiceBloodSa.13. Function of TIM3 May Be Compromised in Human CD4 T-Cells of Untreated Patients with Multiple Sclerosis
Yang L, Anderson D, Hafler D. Sa.13. Function of TIM3 May Be Compromised in Human CD4 T-Cells of Untreated Patients with Multiple Sclerosis. Clinical Immunology 2006, 119: s109. DOI: 10.1016/j.clim.2006.04.245.Peer-Reviewed Original Research
2005
Functional analysis of highly defined, FACS-isolated populations of human regulatory CD4+CD25+ T cells
Baecher-Allan C, Wolf E, Hafler DA. Functional analysis of highly defined, FACS-isolated populations of human regulatory CD4+CD25+ T cells. Clinical Immunology 2005, 115: 10-18. PMID: 15870015, DOI: 10.1016/j.clim.2005.02.018.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, B-LymphocyteCD4-Positive T-LymphocytesCD58 AntigensCoculture TechniquesEnzyme-Linked Immunosorbent AssayFlow CytometryHumansImmunoglobulin GImmunophenotypingLeukocyte Common AntigensL-SelectinReceptors, Interleukin-2Receptors, TransferrinT-Lymphocyte SubsetsConceptsCD4 T cellsT cellsTreg cellsRegulatory cellsTotal CD4 T cellsHuman regulatory cellsRegulatory T cellsAutoimmune disease modelsImportance of CD4Regulatory populationImmune homeostasisCD25Suppressive activityCD4Human regulatorySpecific subpopulationsDisease modelsSignificant proportionMiceVivoMurine cellsPotential heterogeneityFuture studiesCellsHuman diseases
2001
CD4+CD25high Regulatory Cells in Human Peripheral Blood
Baecher-Allan C, Brown J, Freeman G, Hafler D. CD4+CD25high Regulatory Cells in Human Peripheral Blood. The Journal Of Immunology 2001, 167: 1245-1253. PMID: 11466340, DOI: 10.4049/jimmunol.167.3.1245.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAntigens, CDAntigens, DifferentiationB7-1 AntigenB7-H1 AntigenBlood ProteinsCD4 AntigensCD4-Positive T-LymphocytesCells, CulturedCoculture TechniquesCTLA-4 AntigenHLA-DR AntigensHumansImmunoconjugatesImmunosuppressive AgentsInterleukin-2KineticsLeukocyte Common AntigensLymphocyte ActivationLymphocyte CountMembrane GlycoproteinsPeptidesReceptors, Antigen, T-CellReceptors, Interleukin-2RNA, MessengerSignal TransductionT-Lymphocyte SubsetsConceptsRegulatory T cellsRegulatory cellsT cellsPD-1/PD-L1Regulatory CD4 T cellsAnti-CD3 stimulusCD4 T cellsHuman autoimmune disordersMultiorgan autoimmune diseasePeripheral lymphoid tissuesRegulatory cell functionIL-2 receptorPD-L1 receptorCirculation of humansHuman peripheral bloodContact-dependent mannerNeonatal day 3B7 pathwayPD-L1Regulatory populationAutoimmune disordersAutoimmune diseasesPeripheral bloodResponder cellsIL-2
2000
Direct enumeration of Borrelia-reactive CD4 T cells ex vivo by using MHC class II tetramers
Meyer A, Trollmo C, Crawford F, Marrack P, Steere A, Huber B, Kappler J, Hafler D. Direct enumeration of Borrelia-reactive CD4 T cells ex vivo by using MHC class II tetramers. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 11433-11438. PMID: 11005833, PMCID: PMC17217, DOI: 10.1073/pnas.190335897.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBiopolymersBorrelia burgdorferi GroupCD4-Positive T-LymphocytesClone CellsCytokinesDose-Response Relationship, ImmunologicHLA-DR AntigensHLA-DRB1 ChainsHumansIn Vitro TechniquesLipoproteinsLyme DiseaseLyme Disease VaccinesConceptsClass II tetramersMHC class II tetramersT cellsSynovial fluidPeripheral bloodMajor histocompatibility complex class II tetramersTreatment-resistant Lyme arthritisAntigen-reactive T cellsCD4 T cellsDifferent cytokine profilesIL-13 secretionT cell clonesAllogeneic feeder cellsCytokine profileLyme arthritisInflammatory compartmentIL-2IFN-gammaImmunodominant epitopesCell clonesBorrelia burgdorferiPatientsHLABloodCells
1998
Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation.
Scholz C, Patton K, Anderson D, Freeman G, Hafler D. Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation. The Journal Of Immunology 1998, 160: 1532-8. PMID: 9570577, DOI: 10.4049/jimmunol.160.3.1532.Peer-Reviewed Original ResearchMeSH KeywordsAbataceptAntigens, CDAntigens, DifferentiationAutoantigensB7-1 AntigenB7-2 AntigenClone CellsCTLA-4 AntigenEpitopes, T-LymphocyteHumansImmunoconjugatesImmunoglobulin Fc FragmentsImmunosuppressive AgentsInterleukin-4Lymphocyte ActivationMembrane GlycoproteinsMultiple SclerosisMyelin Basic ProteinRecombinant Fusion ProteinsTetanus ToxoidThymidineT-Lymphocyte SubsetsConceptsCD4 T cellsMultiple sclerosisT cellsB7-1Myelin basic proteinPathogenesis of MSMyelin-reactive T cellsPeripheral blood T cellsB7-2 engagementAutoreactive T cellsBlood T cellsAbsence of costimulationCentral nervous systemAntigen-specific signalT cell activationMS patientsB7 costimulationInflammatory diseasesTetanus toxoidB7-2Normal controlsNormal subjectsCostimulatory signalsNervous systemCell activation
1997
Variable Immortalizing Potential and Frequent Virus Latency in Blood-Derived T-Cell Clones Infected With Human T-Cell Leukemia Virus Type I
Richardson JH, Höllsberg P, Windhagen A, Child LA, Hafler DA, Lever A. Variable Immortalizing Potential and Frequent Virus Latency in Blood-Derived T-Cell Clones Infected With Human T-Cell Leukemia Virus Type I. Blood 1997, 89: 3303-3314. PMID: 9129036, DOI: 10.1182/blood.v89.9.3303.Peer-Reviewed Original ResearchConceptsT cell clonesHuman T-cell leukemia virus type IVirus type IT cellsSpontaneous proliferationFresh peripheral blood lymphocytesGag p24 productionCD4 T cellsInfected cellsPeripheral blood lymphocytesHTLV-I provirusViral mRNA expressionType IP24 productionVirus-cell interactionsIL-6Virus carriersInterleukin-6Blood lymphocytesHost cell factorsCytokine mRNAVirus latencyVirus-producing clonesHTLVMRNA expression